[unreadable] Laboratory data suggests that prolactin (PRL), a hormone that controls breast development and lactation, may also play a role in breast carcinogenesis. Data in humans has been sparse consisting of mainly case-control studies with extremely small sample sizes. Only one large prospective study (the Nurses" Health Study) has examined the question, noting a significant positive association between plasma PRL levels similar in magnitude to that of estrogen and breast cancer. If validated, these findings would suggest additional areas for focused research into the development of chemopreventive agents, similar to the development of SERMS for breast cancer prevention. Thus, a large prospective study is urgently needed. The objective of this application is to prospectively evaluate the extent to which PRL levels are related to breast cancer in postmenopausal women. We will specifically test the following hypothesis: Among postmenopausal women, serum prolactin levels are positively associated with breast cancer risk. We will further evaluate the effects of sex steroid hormones and growth factors levels on the prolactin-breast cancer association. As a secondary aim, we will explore the relationship of prolactin levels to clinical characteristics of breast cancer, including tumor stage, grade and ER/PR status. We will undertake a case-cohort study within the Study of Osteoporotic Fractures (SOF). SOF is a prospective study that collected risk factor data and banked fasting serum on 9704 postmenopausal women in the United States. Since 1986, 481 women were diagnosed with breast cancer after enrollment. We will measure prolactin levels in the prospectively-collected serum of 375 women who developed breast cancer during follow-up and 375 SOF participants who did not develop the disease during follow-up. To assess the relationship between prolactin and breast cancer, we will use Cox regression models controlling for covariates such as age, family history, age at first birth, age at menarche, age at menopause, past use of hormone replacement therapy, parity, ever breast fed, and history of benign breast disease, as well as factors affecting prolactin. A positive finding in our study will support the development of breast cancer chemopreventive agents aimed at the prolactin pathway. Approval for this study has already been obtained from SOF and we can begin the study as soon as funding is obtained. [unreadable] [unreadable]